Recent advances in automated robotics, high-resolution digital imaging and image deconvolution software now allow real-time documentation of dynamic processes in living cells and tissues. To take advantage of this progress, we have assembled an accomplished group of senior, mid-career, and junior investigators who wish to apply this emerging technology to their NIH-funded research projects. Together, these six Johns Hopkins faculty members serve as principle investigators on ten different NIH grants including nine R01 grants and one T32 training grant, together accounting for 51 years of cumulative uninterrupted NIH funding. These research projects are funded by six Jdifferent NIH institutes, reflecting a a wide array of research areas, including epithelial and hematopoietic stem cell biology, development biology, developmental neurobiology, macrophage function, and tumor biology. In order to apply recent advances in real time imaging to these projects, the investigators seek to purchase a fully integrated state-of-the-art imaging system comprised of a Zeiss Axiovert-200M motorized inverted fluorescent microscope, a Zeiss AxioCam high-resolution digital camera, a temperature / humidity / CO2-controlled stage chamber for maintenance of viable cell and tissue explants, and sophisticated Zeiss Axioversion software with 3D image deconvolution capability. Together, this Cell Observer System allows dynamic cellular processes to be observed at high resolution using multiple fluorescent channels over extended periods of time, generating new perspectives regarding integrated biologic processes in living tissues. This proposal outlines the scientific rational for use of this sophisticated imaging system, and further describes available institutional support as well as administrative and laboratory resources designed to promote optimal use of this shared instrumentation.